Filling some blanks in a divergent approach to gabosines : enantioselective synthesis of (-)-epiepoxydon, (+)-phyllostine, (-)-gabosine D, and (-)-gabosine E

The levorotatory enantiomers of gabosines D and E were synthesized through a divergent approach that could equally well be applied to the synthesis of the dextrorotatory enantiomers, which have been isolated from natural sources. The approach relies on an initial desymmetrization of p-methoxyphenol, followed by an enzymatic resolution that separately provides the two enantiomers of synthon 3. This versatile synthon can be further transformed into the diverse polyoxygenated cyclohexane target molecules. Key steps in the synthesis of (-)-gabosines D and E from (4R,6S)-3 are the stereoselective hydroxymethylation at the α-carbonyl position leading to (+)-4, and the subsequent reagent-controlled epoxidation of the carbon-carbon double bond. A branching in the sequence also allowed the synthesis of the anhydrogabosines (-)-epiepoxydon and (+)-phyllostine.